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Background: There is a growing burden of non-obese people with diabetes mellitus (DM). However, their cardiovascular risk (CV), especially in the presence of cardiovascular-kidney-metabolic (CKM) comorbidities is poorly characterised. The aim of this study was to analyse the risk of major CV adverse events in people with DM according to the presence of obesity and comorbidities (hypertension, chronic kidney disease, and dyslipidaemia)., Methods: We analysed persons who were enrolled in the prospective Silesia Diabetes Heart Project (NCT05626413). Individuals were divided into 6 categories according to the presence of different clinical risk factors (obesity and CKM comorbidities): (i) Group 1: non-obese with 0 CKM comorbidities; (ii) Group 2: non-obese with 1-2 CKM comorbidities; (iii) Group 3: non-obese with 3 CKM comorbidities (non-obese "extremely unhealthy"); (iv) Group 4: obese with 0 CKM comorbidities; (v) Group 5: obese with 1-2 CKM comorbidities; and (vi) Group 6: obese with 3 CKM comorbidities (obese "extremely unhealthy"). The primary outcome was a composite of CV death, myocardial infarction (MI), new onset of heart failure (HF), and ischemic stroke., Results: 2105 people with DM were included [median age 60 (IQR 45-70), 48.8% females]. Both Group 1 and Group 6 were associated with a higher risk of events of the primary composite outcome (aHR 4.50, 95% CI 1.20-16.88; and aHR 3.78, 95% CI 1.06-13.47, respectively). On interaction analysis, in "extremely unhealthy" persons the impact of CKM comorbidities in determining the risk of adverse events was consistent in obese and non-obese ones (P int =0.824), but more pronounced in individuals aged < 65 years compared to older adults (P int = 0.028)., Conclusion: Both non-obese and obese people with DM and 3 associated CKM comorbidities represent an "extremely unhealthy" phenotype which are at the highest risk of CV adverse events. These results highlight the importance of risk stratification of people with DM for risk factor management utilising an interdisciplinary approach., (© 2024. The Author(s).)

Background: A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up., Methods: We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months., Results: The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p =0.002; 23.7% at baseline versus 39.6% at LFUV, p <0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p =0.035; 33.8% at baseline versus 54.0% at LFUV, p <0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p =0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p =0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p =0.02) than males. At LFUV, a similar sex-related pattern was observed., Conclusion: Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Puglisi, Barač Nekić, Morelli, Alessi, Fosci, Pani, Zibar Tomsic, Palmieri, Ferraù, Pia, Chiodini, Kastelan, Reimondo and Terzolo.)

Background: Cardiometabolic health has become crucial, especially for women with HIV (WWH). We assessed the achievement of targets for hypertension, dyslipidemia, and diabetes (H/Dy/DT) in primary prevention in a WWH cohort., Methods: Cross-sectional analysis including all WWH in our clinic, excluding those who had a myocardial infarction. H/Dy/DT achievement was assessed by both EACS guidelines and individual cardiovascular risk, CVR (measured by ESC calculator), using logistic regression to evaluate differences in H/Dy/DT achievement between migrant and Italian women., Results: We included 292 WWH, 55.5% Italian and 44.5% migrant women; the median age was 50 (IQR:42-58) years, 94.5% had undetectable HIV-RNA, 55.1% had a high level of education, 27.1% were smokers, and 19.2% did regularly physical exercise. Overall, 76%, 19%, and 5% of women presented a low, a high, and a very high CVR, respectively. Among Italians, 28.4% and 6.2% women presented a high and a very high CVR, respectively. Considering migrants, 7.7% and 3.8% women presented a high and a very high CVR, respectively. Overall, among migrant women, those with a high CVR were more likely to be not at target than those with a low risk (especially for LDL-c and blood pressure among people on treatment), despite the fact that we did not detect a statistically significant difference. By contrast, migrants were more likely to achieve glycemic targets than Italians ( p = 0.032)., Conclusions: H/Dy/DT target achievement is suboptimal, especially in migrants. A more aggressive pharmacological treatment, also assessing adherence to medical prescriptions, and promotion of healthy lifestyle should be urgently implemented, possibly redrawing the current model of care.

Dyslipidemia is the most frequent cardiovascular (CV) risk factor in able-bodied athletes and is frequently undertreated, resulting in an underestimated risk of atherosclerosis-related diseases. Data on lipid profile in Paralympic athletes are lacking. Our study aimed to identify the prevalence of dyslipidemia and the influence of disability type and sporting discipline in Paralympic athletes. We evaluated 289 athletes who participated in the Paralympic Games from London 2012 to Beijing 2022. All athletes underwent clinical/physical evaluation, blood tests, and body composition analysis. They were divided into different groups based on sports disciplines and disability type (spinal cord injuries [SCIs] and non-SCIs [NSCIs]). Among the Paralympic athletes, 34.6% had a low-density lipoprotein (LDL) level ≥115 mg/100 ml. They were older (38.1 ± 9.2 vs 30.6 ± 9.6, p = 0.001) and had a higher CV risk. Athletes with SCI showed similar total cholesterol and triglycerides, higher LDL (110.9 ± 35.2 vs 102.7 ± 30.6 mg/100 ml, p = 0.03) and lower high-density lipoprotein (HDL) (53.6 ± 13.6 vs 60.5 ± 15.4 mg/100 ml, p = 0.001) than those with NSCI. Endurance athletes had lower LDL, the highest HDL, and the lowest triglycerides and LDL/HDL ratio compared with other sports disciplines. A mean follow-up of 61.5 ± 30.5 months was available in 47% athletes, and 72.7% of the athletes with dyslipidemia continued to present altered LDL values at follow-up. In conclusion, dyslipidemia is the most common CV risk factor in the Paralympics, affecting 35% of athletes, with only mild lipid changes over a medium-term time. The type of disability and sporting discipline has an impact on lipids, improving HDL and reducing LDL, with a better profile observed in NSCI and endurance athletes., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death., Methods: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February-December 2020. Multivariate logistic regression identified the mortality risk factors., Results: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07-14.76), obesity (adjOR 8.58, CI 3.30-22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06-94.22), heart disease (adjOR 17.68, 95% CI 3.80-82.18), cancer (adjOR 13.28, 95% CI 4.25-41.51) and male sex (adjOR 5.24, 95% CI 2.30-11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients., Conclusion: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals' death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.

Purpose: COVID-19 pandemics and cardiometabolic health are mutually interconnected. Chronic metabolic diseases are known risk factors for increased mortality after SARS-CoV-2 infection. In turn, COVID pandemics imposed sudden changes in lifestyle and social isolation with consequent potential cardiometabolic sequelae. The present study aimed at investigating the impact of changes in lifestyle and social life on metabolic profile in hyperprolactinemic or osteoporotic patients without pre-existing cardiometabolic diseases at the time of COVID-19., Methods: The primary study outcome measurement was the prevalence of obesity, arterial hypertension, impaired glucose tolerance (IGT) or diabetes mellitus (DM), dyslipidemia and metabolic syndrome after COVID-19 outbreak. Seventy-four patients (21 men and 53 women, aged 51.8 ± 17.8 years) were admitted to the outpatient clinic of the Neuroendocrine Disease Unit at University "Federico II" of Naples, Italy, as per their routine clinical practice because of tumoral and non-tumoral hyperprolactinemia in 52 patients (70.3%), and osteoporosis/osteopenia in 22 (29.7%). Among female patients, 25 (47.2%) were at menopausal age., Results: At the end of lockdown, prevalence of obesity (from 37.8% to 51.3%, p < 0.0001), dyslipidemia (from 28.4 to 48.6%, p = 0.003) and metabolic syndrome (from 14.9 to 27%, p < 0.0001) significantly increased compared to pre-COVID evaluation. No significant change was found in the prevalence of arterial hypertension and IGT/DM., Conclusion: SARS-CoV-2 outbreak has led to a rapid increase in the prevalence of metabolic syndrome, potentially contributing to the increased COVID-19 related mortality., (© 2021. The Author(s).)

Background: This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients., Methods: We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone., Results: We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78-100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from - 3 to - 11%, p < 0.001, HIS + ezetimibe vs. HIS-from - 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a "treat to absolute LDL-cholesterol levels" approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention., Conclusions: Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention., (© 2021. The Author(s).)

Purpose: Early adoption of a healthy lifestyle has positive effects on cardiovascular health (CVH) in adulthood. In this study, we aimed to assess CVH metrics in a cohort of healthy teenagers with focus on differences between rural and urban areas., Methods: The Early Vascular Aging (EVA) Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Data from the baseline and control group (prior to health intervention) are included in the current analysis. CVH determinants (smoking, body mass index, physical activity, dietary patterns, systolic and diastolic blood pressure, total cholesterol and fasting blood glucose) were assessed and analyzed for urban and rural subgroups separately by univariate testing. Significant variables were added in a generalized linear model adjusted for living in urban or rural area with age and sex as covariates. Ideal CVH is defined according to the guidelines of the American Heart Association., Results: 2031 healthy adolescents were enrolled in the present study (56.2% female, mean age 16.5 years). 792 adolescents (39.0%) were from urban and 1239 (61.0%) from rural areas. In 1.3% of adolescents living in urban vs. 1.7% living in rural areas all CVH determinants were in an ideal range. Compared to the rural group, urban adolescents reported significantly longer periods of moderate to vigorous-intensive activity (median 50.0 min/day (interquartile range 30-80) vs. median 40.0 min/day (interquartile range 25-60), p < 0.01). This observation remained significant in a generalized linear model (p < 0.01). There were no significant differences between the study groups regarding all other CVH metrics., Conclusion: The low prevalence of ideal CVH for adolescents living in urban as well as rural areas highlights the need for early health intervention. Geographic differences must be taken into account when defining targeted subgroups for health intervention programs., (© 2021. The Author(s).)

Background: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals., Methods: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h., Results: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes., Conclusions: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study.

Background and Aims: CA.ME.LI.A (CArdiovascular risks, MEtabolic syndrome, LIver and Autoimmune disease) is a cross-sectional, epidemiological study performed between 2009-2011 in Abbiategrasso (Milan, Italy) to estimate the prevalence of cardiovascular risk factors, metabolic syndrome, liver and autoimmune diseases in the general adult population. This report focuses on the description and presentation of baseline characteristics of the population., Methods and Results: Citizens were randomly selected from the city electoral registers (n = 30903), yielding a sample of 2554 subjects (M = 1257, F = 1297; age, 47 ± 15 yrs; range 18-77 yrs). Men had higher prevalence of overweight or obesity (60.8% vs 41.6%; p < 0.0001) and greater thickness of visceral adipose tissue (40 ± 19 vs 27 ± 17 mm; p < 0.0001); no gender difference was found in subcutaneous adipose tissue thickness. Men also showed higher levels of serum triglycerides, γ-GT, fasting blood glucose, insulin and Homa-IR Index, while HDL, CRP, and prevalence of elevated (>5.0 mg/L) CRP were lower. Compared to normal weight men, risk-ratio (RR) of CRP elevation was 1.32 (ns) in overweight and 2.68 (p < 0.0001) in obese subjects. The corresponding figures in females were 2.68 (p < 0.0001) and 5.18 (p < 0.0001). Metabolic syndrome was more frequent in men (32.7% vs 14.5%; RR: 2.24, p < 0.0001). Interadventitia common carotid artery diameter was higher in men and increased with age and BMI., Conclusions: The present study reports on the overall characteristics of a large population from Northern Italy. It aims to identify the associations among cardiovascular risk factors to prevent their development and progression, improve healthy lifestyle and identify subjects liable to pharmacological interventions., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The well-established benefit of Low-Dense-Lipoprotein-cholesterol (LDL-c) lowering treatments (LLTs) has led clinical guidelines to lower the cardiovascular prevention targets. Despite this, there is a surprising scarcity of real-world studies (RWS) evaluating whether recommendations are applied in the routine clinical management of patients with type 2 diabetes (T2D). We therefore evaluated, in a large RWS, the pattern of LLTs use and the achievement of LDL-c targets in patients with T2D in Italian diabetes specialist clinics., Methods: We collected data from 46 diabetes outpatient clinics (following 281,381 subjects), including 104,726 T2D patients, for whom use of LLTs between 2015 and 2016 was ascertained. We used the 2016 and 2019 European Atherosclerosis Society and European Society of Cardiology (EAS-ESC) guidelines to define cardiovascular risk categories, LDL-c targets, and the expected LDL-c reduction and cardiovascular benefit achievable with LLT intensification., Results: 63,861 patients (61.0%) were on statin therapy, 9.2% of whom were also on ezetimibe. Almost all subjects were at high (29.3%) or very high (70.4%) cardiovascular risk, including 17% being in secondary prevention. Among very high-risk patients, 35% were not on statin despite half of them had LDL-c > 2.6 mmol/l, and only 15% of those on statins had LDL-c < 1.4 mmol/l. 83% of subjects in secondary prevention were on a statin, but half of them had LDL-c > 1.8 mmol/l. Overall, 35% and 14% of subjects achieved the LDL-c targets as suggested by 2016 and 2019 EAS-ESC Guidelines, respectively. Based on anticipated response to treatment, we estimated that 38% of the entire population would require high-intensity-statin (HI-statin), 27% a combination of HI-statin plus ezetimibe, and 27% the addition of proprotein-convertase-subtilisin/kexin-9 (PCSK9) inhibitors. These LLT intensifications would reduce the incidence of cardiovascular events by 32%, from 23.511 to 16.022 events per 100.000 patients/10-years (incidence-rate-ratio 0.68; 95% C.I 0.67-0.70, p < 0.001)., Conclusions: Despite the increase in use of LLT in T2D over the last decades, a large proportion of subjects with T2D did not achieve their LDL-c targets. Given the very high cardiovascular risk of these patients, improving LLT is expected to have a dramatic impact on cardiovascular event prevention.

Background: Coronavirus Disease 2019 (COVID-19) causes severe complications and deaths all over the world. COVID-19 also has indirect effects from the lockdown and the possible lack of food. We aimed to evaluate the perception of this in Celiac Disease (CeD) patients who require a lifelong gluten-free diet as a therapy., Methods: We invited by e-mail CeD adult patients from the University of Salerno (Campania, South Italy) and the University of Padua (Veneto, North Italy) to answer an ad hoc COVID-19 survey., Results: We sent the web survey to 651 email addresses and we received 276 answers (42,4%). CeD patients did not feel more vulnerable because they had CeD ( not at all 56.6%) and they did not worry much about the possible shortness of gluten-free food during the epidemic ( not at all 48.5%). The most worried were the elderly patients, patients with other comorbidities and females. Finally, CeD patients were happy with remote consultations and explicitly asked to have them., Discussion: The COVID-19 pandemic has impacted a proportion of patients with CeD; in particular, women, elderly patients, patients with other comorbidities. COVID-19, although a challenging experience from the medical and the psychological point of view, has offered an opportunity to practice, on a large-scale, a remote consultation approach for CeD healthcare., Competing Interests: None, (© 2020 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.)

Le linee guida 2019 delle Società europee di cardiologia e dell'aterosclerosi sulla gestione delle dislipidemie hanno aumentato l'aggressività diagnostico-terapeutica e non distinguono prevenzione primaria e secondaria, con parziale eccezione per gli ultra75enni. Raccomandano nuovi target di cLDL: per pazienti a rischio molto alto si raccomanda una riduzione a <55 mg/dl e >=50% rispetto al basale; per pazienti a rischio alto una riduzione a <70 mg/dl e >=50% del basale; per pazienti a rischio moderato una riduzione a <100 mg/dl; per pazienti a rischio basso una riduzione a <116 mg/dl. In base alle carte SCORE e ai dati di mortalità cardiovascolare in Italia, quasi tutti i maschi dai 70 anni e le donne dai 70-75 anni risulterebbero ad alto rischio per solo effetto dell'età. Anche quasi tutti i 60enni sarebbero a rischio moderato, con target di cLDL <100, e spesso necessità di aggiungere costosi ipolipemizzanti per chi già assume statine. Le prove supportano ben poco tale aggressività. Infatti, anche negli studi randomizzati controllati (RCT) i benefici su esiti cardiovascolari non fatali subiscono esagerazioni sistematiche, quello meno distorto e di maggior interesse per gli assistiti è la mortalità totale. Questa, con terapie ipocolesterolemizzanti più intensive, non si è ridotta nelle metanalisi di RCT con pazienti con cLDL tra 80 e <100 mg/dl al basale; con inibitori di PCSK9, pazienti con questi valori mostrano persino tendenza all'aumento della mortalità totale. Dunque, abbassare il cLDL a <80 mg/dl può non giovare neppure ad anziani coronaropatici. A oggi, ciò vale ancora di più per anziani nella popolazione generale, in cui una revisione sistematica di studi di coorte ha mostrato relazioni nulle o più spesso inverse tra cLDL e mortalità. Le nuove linee guida europee forzano le prove disponibili, trascurano il principio di precauzione e non possono esser base per un equo consenso informato.

Introduction: Age is traditionally considered a major cardiovascular (CV) risk factor, but its real weight in the absence of other modifiable risk factors is not clear., Aim: To compare the prevalence of subclinical carotid atherosclerosis, and its association with the main CV risk factors, between older adults and hypertensive adults., Methods: Cross-sectional study on 210 consecutive patients: 70 older adults (age ≥ 80 years), and 140 hypertensive adults having at least another CV risk factor. Patients had no history of peripheral artery disease or major CV events., Results: Mean age was 54.2 ± 7.2 years in hypertensive adults and 88.5 ± 5.5 years in older adults with a female prevalence in the latter group. Dyslipidemia and smoking were more prevalent in hypertensive adults, while chronic kidney disease was more prevalent in older adults. Prevalence of carotid plaques did not differ between hypertensive adults and older adults (48.2% vs 55.6%, respectively, p = 0.311). Age ≥ 80 years was not associated with a higher risk of carotid plaques even after adjusting for other risk factors (p = 0.204). Hypertension and dyslipidemia were the risk factors more strongly associated with carotid plaques in older adults and hypertensive adults, respectively. When older adults with hypertension were excluded from the analysis, prevalence of carotid plaques was significantly higher in hypertensive adults (p = 0.042)., Conclusion: Hypertension and dyslipidemia are the major determinant of atherosclerosis regardless of age in our study. Our findings support the concept that aging is not necessarily synonymous with atherosclerosis and highlight the key role played by superimposed CV risk factors on arterial ''bad aging''.

The aim of this study is to evaluate whether nutrients intake in an Italian adult population receiving pharmacological treatment for hypertension, dyslipidemia, and diabetes are within the recommended values proposed by dietary guidelines. Cross-sectional data from the Cardiovascular Epidemiology Observatory/Health Examination Survey in 8462 individuals 35-79 years were used. Food consumption was assessed with a self-administered semi-quantitative food frequency questionnaire. Dietary sodium and potassium intakes were measured in 24-hour urine collection. Recommendations from WHO were used for salt and potassium intakes, those from the Diabetes and Nutrition Study Group for diabetes, and those from the European Society of Cardiology for hypertension and dyslipidemia. Salt intake in urine collection of participants receiving treatment for hypertension was 11.1 ± 4.0 g/day for men and 8.6 ± 3.3 g/day for women, higher than recommended. In participants treated for dyslipidemia, mean saturated fat intake was 11.4% and 11.6% total Kcal in men and women respectively, higher than recommended, while cholesterol intake was higher only in men (365.9 ± 149.6 mg/day). In both men and women receiving treatment for diabetes, mean intake of saturated fats (12.3% and 12.2% of total Kcal), simple carbohydrates (17.5% and 19.8% of total Kcal) and cholesterol (411.0 ± 150.4 and 322.7 ± 111.1 mg/day) were above the recommendations, while fiber intake was below (19.5 ± 6.3 and 17.5 ± 6.2 mg/day). Overall, 70% to 80% of participants treated for these conditions received advice from family doctors on dietary management; however, nutrition is far from being optimal.

Background: The use of extended criteria donors (ECD) in liver transplantation is increasing due to the organ shortage. Histological evaluation of the liver graft in the context of procurement is an important tool for extending the donor pool without affecting the quality of the transplanted organs. Macrovesicular steatosis is widely accepted as predictor of early allograft dysfunction (EAD), while other features, such as portal fibrosis, are poorly studied., Aim: To identify morphological features, other than macrovesicular steatosis, that may affect recipients' outcome., Methods: Between 2014 and 2016, 132 donors with extended criteria underwent pre-transplant liver biopsy during procurement. Histological variables of the graft, donors'/recipients' clinical data, EAD and patient/graft survival were registered., Results: The recipients who received a graft with histological-proven portal fibrosis had a significant lower patient and graft survival in comparison to patients without fibrosis (P = 0.044 and P = 0.039, respectively). Donors' dyslipidemia was significantly associated with the occurrence of EAD (P = 0.021). When dyslipidemia was combined with histological liver fibrosis a 54.5% incidence of EAD was observed (P = 0.012)., Conclusions: The histological assessment of liver fibrosis in pre-transplant biopsy of ECD grafts, together with donor's clinical data, provides important information on recipients' outcome., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The current use of lipid lowering therapies and the eligibility for proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors of patients surviving a myocardial infarction (MI) is poorly known., Methods: Using the data from two contemporary, nationwide, prospective, real-world registries of patients with stable coronary artery disease, we sought to describe the lipid lowering therapies prescribed by cardiologists in patients with a prior MI and the resulting eligibility for PCSK9 inhibitors according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) and the Italian regulatory agency (Agenzia Italiana del Farmaco; AIFA) criteria. The study cohort was stratified according to the following low-density lipoprotein cholesterol (LDL-C) levels at the time of enrolment: <70 mg/dl; 70-99 mg/dl and ≥100 mg/dl., Results: Among the 3074 post-MI patients with LDL-C levels available, a target level of LDL-C < 70 mg/dl was present in 1186 (38.6%), while 1150 (37.4%) had LDL-C levels ranging from 70 to 99 mg/dl and the remaining 738 (24.0%) an LDL-C ≥ 100 mg/dl. A statin was prescribed more frequently in post-MI patients with LDL-C levels <70 mg/dl (97.1%) compared to the other LDL-C groups ( p < 0.0001). A low dose of statin was prescribed in 9.3%, while a high dose in 61.4% of patients. Statin plus ezetimibe association therapy was used in less than 18% of cases. In the overall cohort, 293 (9.8%) and 450 (22.2%) resulted eligible for PCSK9 inhibitors, according to ESC/EAS and AIFA criteria, respectively., Conclusions: Post-MI patients are undertreated with conventional lipid lowering therapies. A minority of post-MI patients would be eligible to PCSK9 inhibitors according to ESC/EAS guidelines and Italian regulatory agency criteria., Competing Interests: All authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Dr De Luca and Dr Temporelli received speakers fees from Menarini, outside the submitted work., (Copyright © 2020 Furio Colivicchi et al.)

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18-22) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in -vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and -vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women.

Objectives: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014., Methods: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow-up). We used the χ 2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time., Results: The closed cohort included 1517 participants and the open cohort 3668 under follow-up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37-46] years in 2004 and 44 (IQR 36-52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m 2 in 2004 versus 30% in 2014); the percentage of people in the high-risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar., Conclusions: The burden of NCDs in our PLWHIV population markedly worsened over a 10-year time-span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs., (© 2018 British HIV Association.)

Aims: The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe., Methods: The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile. Distribution of LLTs and LDL-C target attainment were assessed. Multivariate logistic regression evaluated predictors of LDL-C target attainment. A 24% LDL-C lowering was modeled in patients not taking ezetimibe to assess its potential effects., Results: Among 676 Italian CHD patients enrolled, LDL-C concentrations were lower among the 631 patients (93.3%) who were on LLT (82 versus 118 mg/dl; P < 0.001). The LDL-C target was attained by 35.4% of patients. Statin dose (median atorvastatin dose 40 mg/day) was the sole significant predictor of LDL-C target attainment. The simple addition of ezetimibe in the model reduced the percentage of patients more than 70 and 100 mg/dl from 64.6 to 37.9% and from 25.1 to 11.8%, respectively., Conclusion: Despite treatment in more than 90%, only one-third of Italian stable CHD patients attained the recommended LDL-C target. Statin dose was the sole predictor of the target achievement. The addition of ezetimibe would almost double patients at target and halve the potential candidates for reimbursement of more expensive agents such as proprotein convertase subtlisin/kexin type 9 inhibitors.

Aims: Cardio50 is a project of active risk identification and cardiovascular prevention implemented in an Italian cohort of healthy people aged 50., Methods: A total of 3127 individuals were invited for a screening visit with lifestyle interview and registration of BMI, blood pressure (BP), glucose, cholesterol and classified into groups: A (normal), B (abnormal lifestyle, normal parameters), C (at least one abnormal parameter). People in group C were offered a free blood test and a specialistic medical visit to investigate the suspect of hypertension, dyslipidemia or dysglycemia. Those in groups B and C were scheduled for a follow-up visit after 4-6 months and finally readdressed to the general practitioner., Results: A total of 2325 invited individuals attended the screening visit: 18% were classified in group A, 32% in B, 42% in C, 8% met exclusion criteria and were not classifiable. In group C, 86% attended to the cardiologist visit, 76% had dyslipidemia, 35% hypertension, 1% diabetes, 14% impaired fasting glycemia, 19% obesity, 21% metabolic syndrome; 21% were smokers, 11% at risk of alcoholism. At follow-up, we appreciated a decrease in BP in group C individuals. After lifestyle intervention, physical activity increased, whereas metabolic syndrome, impaired fasting glucose and risky drinking decreased., Conclusion: The current project is coherent with modern strategies based on multifactorial actions. After the intervention, we observed an early reduction in BP and some improvements in lifestyle. This simple and low-technology program allowed us to detect and treat large numbers of individuals at high risk for cardiovascular events.

Objective: The aim of the present study was to investigate the prevalence of abnormal cholesterol levels and to explore awareness of cholesterol values in an unselected sample of community-living adults., Design: Cross-sectional survey., Setting: Exhibitions, malls and health promotion campaigns across Italy., Participants: 3535 community dwellers aged 18-98 years were enrolled between September 2016 and June 2017. Analyses were conducted in 3040 participants, after excluding 495 enrolees on cholesterol-lowering medications., Main Outcome Measures: Total blood cholesterol levels and awareness of cholesterol values., Results: Abnormal blood cholesterol values were found in 1961 (64.5%) of participants with no differences between genders (p=0.06). Among those who believed they had normal cholesterol levels, only 48% had values below 200 mg/dL. More than 40% had cholesterol values between 200 and 240 mg/dL, and around 10% had values >240 mg/dL. More than one-third of participants had not measured cholesterol in the last year. Among them, only 36% had normal cholesterol levels., Conclusions: Abnormal blood cholesterol is highly prevalent in our sample of Italian community dwellers, with less than half of participants being aware of their cholesterol levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The association of metabolic syndrome (MetS) traits with urinary calcium (UCE) or oxalate excretion (UOE) is uncertain in calcium stone formers (CSFs). Our aim was to investigate this association in a large group of Caucasian CSFs., Methods: We retrospectively reviewed data of CSFs evaluated at our Kidney Stone Clinic from 1984 to 2015. Data on body mass index (BMI), MetS traits defined according to international consensus, family history of urolithiasis, anti-hypertensive treatments, calcemia, renal function, and 24-h urinary profile of lithogenic risk were collected. The association between MetS traits and UCE or UOE was tested with multivariate linear regression models accounting for a long list of potential confounders., Results: We included 3003 CSFs, aged 44 ± 14 years. The prevalence of hypertension, diabetes, overweight (BMI ≥ 25 kg/m 2 ) and dyslipidemia was 17, 2, 42 and 38%, respectively. Median values of UCE and UOE were 211 mg/24 h (IQR 143-296) and 28 mg/24 h (IQR 22-34), respectively. At a multivariate model, including age, sex, date of examination, drug treatments, family history, renal function, blood calcium and urinary factors as covariates, hypertension was a significant positive determinant of UCE (β ± SE 0.23 ± 0.07, p = 0.003), but overweight, dyslipidemia and diabetes were not. No MetS trait was significantly associated with UOE in multivariate models., Conclusions: In a large group of Caucasian CSFs, hypertension was the only MetS trait significantly associated with UCE, while no MetS trait was associated with oxalate excretion.

Background and Aims: Statin utilization and lipid goal achievement were estimated in a large sample of Italian patients at high/very-high cardiovascular (CV) risk., Methods: Patients aged ≥18 years with a valid low-density lipoprotein cholesterol (LDL-C) measurement in 2015 were selected from the IMS Health Real World Data database; non-high-density lipoprotein cholesterol (non-HDL-C) was assessed in those with available total cholesterol measurements. Index dates were defined as the last valid lipid measurement in 2015. Patients were hierarchically classified into mutually exclusive risk categories: heterozygous familial hypercholesterolemia (primary and secondary prevention), atherosclerotic CV disease (including recent acute coronary syndrome [ACS], chronic coronary heart disease, stroke, and peripheral arterial disease), and diabetes mellitus (DM) alone. Statin and non-statin lipid-modifying therapy (LMT) use, and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline-recommended goal attainment, were assessed., Results: Among 66,158 patients meeting selection criteria, the overall rate of LMT prescriptions was 53.3%, including 7.7% on high-intensity statin therapy. Statin use was highest for recent ACS and lowest for DM alone. LDL-C goal attainment was 16.0% for <1.8 mmol/l and 45.0% for <2.5 mmol/l; 24.3% reached non-HDL-C <2.6 mmol/l and 52.2% were at <3.3 mmol/l. Goal achievement was greatest with high-intensity statin use., Conclusions: Statin use in this cohort was consistent with previous reports in Italian patients at high/very-high CV risk, and low relative to statin use in other European countries. The low rate of ESC/EAS lipid goal attainment observed was consistent with outcomes of other European studies., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lack of adequate management of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. This study assessed the clinical management and outcome of stages 1-5 CKD patients., Methods: Patients were prospectively followed for 3 years in 25 nephrology centers across Italy. Clinical characteristics were measured at baseline and every 6 months. Outcome measures included CKD staging, presence of comorbidities, treatment, mineral bone disorder (MBD) parameters, and patient outcomes., Results: Of 884 enrolled patients (59.7% males, aged 66.2 ± 14.6 years), 587 (66.4%) completed the study. The majority of patients were referred by a general practitioner (44.7%) and had stage 3 or 4 CKD (40.9 and 23.8% respectively). Data reveal that 91.3% of patients had at least 1 concomitant disease, most frequently hypertension (80.1%) and dyslipidemia (42.5%); 94.6% of patients were receiving cardiovascular medication and 52.6% were receiving lipid-lowering medication. Approximately 40% of patients had proteinuria and intact parathyroid hormone levels outside the normal range. As expected, stages 4 and 5 CKD patients had a higher prevalence of proteinuria (68 and 74%), MBD (59 and 88%) and anemia (28 and 73%), as well as a higher risk of hospitalization (34.3 and 51.9%) and need for dialysis (69.5 and 70%). The overall probability of survival over 36 months was 90.6%., Conclusions: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount., (© 2018 S. Karger AG, Basel.)

Background: Surveillance of and monitoring trends for cardiovascular diseases and risk factors are relevant when we consider that these diseases and conditions are largely preventable. The aim of this paper is to assess time trends of cardiovascular diseases, lifestyles, risk factors and high risk conditions in different socioeconomic levels., Methods: Paired but independent population samples of men and women aged 35-74 years located in all 20 Italian regions were examined in 1998-2002 (n = 9612) and in 2008-2012 (n = 8141). Time trends of lifestyles, cardiovascular risk factors, prevalence of high-risk conditions and cardiovascular diseases are shown for two different socioeconomic levels, as assessed by educational level., Results: Over 10 years, in both genders and socioeconomic classes, the prevalence of smoking decreased (from 32% to 23% in men) as well as mean levels of blood pressure (systolic from 136 mmHg to 133 mmHg in men and from 132 mmHg to 127 mmHg in women), while the prevalence of dyslipidemia and obesity increased reaching 35% and 25% of the population respectively; the prevalence of myocardial infarction remained stable (1.6% in men; about 0.5% in women), that of stroke decreased in men (from 1.2% to 0.7%); the prevalence of diabetes did not change (12% in men; 8% in women). In the low educational class, cardiovascular risk factors and diseases remained unfavourable compared with the high educational class., Conclusions: The burden of cardiovascular diseases and their risk factors remain high and require continuous appropriate action at the community and individual levels, as suggested by the European Guidelines for Cardiovascular Prevention., (© The European Society of Cardiology 2015.)

Background: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability., Methods and Results: In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels., Conclusions: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: The epidemiology of cardiovascular risk (CV) in the elderly is far from being defined, and the reasons why some subjects retain a healthy body while growing old while others are affected by different diseases or die prematurely are still unknown., Aims: To compare the CV risk pattern in two elderly cohorts living in North-East Italy., Materials and Methods: The Risk Of Vascular complications: Impact of Genetics in Old people (ROVIGO) study is a population-based study including 580 unrelated elderly subjects representative of general population living in Rovigo in the Veneto region. They were compared to a cohort of 580 age-gender-matched unrelated subjects from the CArdiovascular STudy in the Elderly (CASTEL) living in the same region in Castelfranco Veneto and Chioggia., Results: Blood pressure (BP), heart rate (HR), low-density-lipoprotein cholesterol, and prevalence of coronary heart disease, heart failure and chronic pulmonary disease were lower in the ROVIGO than in the CASTEL cohort, while high-density-lipoprotein cholesterol and the prevalence of diabetes were higher in the former than in the latter. In the ROVIGO cohort, diabetes, left ventricular hypertrophy, coronary and cerebrovascular diseases were more represented in men. In the CASTEL cohort, systolic BP was higher in women. In both cohorts, the lipid pattern was less favourable and HR higher in women, chronic pulmonary disease more represented in men., Conclusions: People living in Rovigo were at lower CV risk than those in Castelfranco Veneto and Chioggia, mainly due to lower BP values, better lipid pattern and lower prevalence of CV and pulmonary disease.

Background: Control of hypertension remains a major unmet need, worldwide., Hypothesis: To test whether the presence of hypertension may improve global cardiovascular (CV) risk stratification and achievement of therapeutic targets for CV risk factors in adult outpatients in Italy., Methods: Physicians were asked to submit data covering the first 10 consecutive adult outpatients. All data were centrally analyzed for global CV risk assessment and rates of control of major CV risk factors, mostly blood pressure (BP) levels, in different high-risk subgroups of hypertensive patients., Results: Overall, 1078 physicians collected data of 9864 outpatients (46.7% females, age 66.1 ± 10.3 years) with valuable data on BP levels, among which 7147 (72.5%) had a diagnosis of hypertension and 2717 (27.5%) were normotensive subjects. Hypertensive patients were older and had a higher prevalence of major risk factors, including smoking, obesity, dyslipidemia, and family history of cardiovascular disease, as well as comorbidities, than did normotensive subjects (P < 0.001 for all comparisons). Despite worse control of BP (66.9% vs 36.2%, P < 0.001), high-density lipoprotein cholesterol (40.5% vs 37.4%, P < 0.005), triglycerides (72.1% vs 67.8%, P < 0.001), and fasting plasma glucose (71.2% vs 67.0%, P < 0.005), hypertension was associated with larger availability and frequency of diagnostic examinations and greater use of antihypertensive, glucose-lowering, and lipid-lowering drugs, as well as antiplatelet agents, compared with normotension (P < 0.001)., Conclusions: Presence of hypertension significantly improved clinical data collection and CV risk stratification. Such an approach, however, was not paralleled by better control of major CV risk factors., (© 2015 Wiley Periodicals, Inc.)

Background: Atypical antipsychotics are the main treatment for a large number of psychiatric illnesses, with fewer extrapyramidal effects than conventional antipsychotics. However, it has been suggested that their use is associated with increased risk of dyslipidemia and type 2 diabetes mellitus., Objective: The risk of metabolic adverse effects associated with asenapine was assessed in comparison with that associated with olanzapine using real-world data., Methods: This study was a retrospective analysis based on data extracted from the Italian and Spanish Cegedim Strategic Data Longitudinal Patient-Data databases. Patients with asenapine or olanzapine prescriptions were retrieved from September 2010 to December 2012 using strict inclusion criteria to guarantee minimization of confounders. Patients with type 2 diabetes mellitus and dyslipidemia were identified by using ICD9 codes and by antidiabetic and dyslipidemic drug prescriptions. The presence or absence of the metabolic condition was compared before and after treatment, and between cohorts., Results: The retrospective analysis showed a lower risk of developing type 2 diabetes with asenapine than with olanzapine (2.2 vs 3.5%, respectively; p value: 0.0002) and of developing dyslipidemia (2.8 vs 6.8%, respectively; p value: 0.0001)., Conclusions: Asenapine is associated with a lower risk of metabolic adverse effects than olanzapine, demonstrating its improved safety profile.

Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers., Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196°C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method., Results: The highest tertiles of total (HR 1.66, 95%CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95%CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer., Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In Italy, patients with dyslipidemia account for 15-20% of the adult population with major healthcare and socio-economic impact. According to the ESC/EAS guidelines for the management of dyslipidemias, desirable cholesterol and triglyceride levels can be achieved with a synergy between drug treatment and adequate diet therapy. However, what diets should be adopted? In this review article, different types of dietary treatments are compared, with a special focus on diet education. The new scientific frontier of nutrigenetics is also discussed.

Background: The request to lose weight is expanding not only in obese and morbidly obese patients but also in overweight patients affected by co-morbidities as diabetes and hypertension and who do not tolerate diet regimen or lifestyle changes. The aim of this study is a multicenter evaluation of outcomes of intragastric balloon in overweight patients., Methods: Patients (BMI 27-30 kg/m2) treated with a BioEnterics Intragastric Balloon (BIB) between 1996 and 2010 were extracted from the database of the participating centres in Rome (Italy), Liège (Belgium) and Madrid (Spain). Primary endpoints were the efficacy and safety at 6 and 42 months from balloon positioning. Secondary endpoints included resolution of co-morbidities., Results: A total of 261 patients were included in this study. The most common indication for balloon placement was a psychological disorder (54%). Mean body mass index (BMI) fell from 28.6 ± 0.4 at baseline to 25.4 ± 2.6 kg/m2 at 6 months and to 27.0 ± 3.1 kg/m2 at 3 years from BIB removal. The mean %EWL was 55.6% at 6 months and 29.1% at 3 years. Forty-seven patients (18%) had complications associated with placement of the intragastric balloon (leak = 28, intolerance = 14, duodenal ulcer = 2, gastritis = 1, oesophagitis = 1, duodenal polyps = 1). The rate of patients with hypertension decreased from 29% at baseline to 16% at 3 years. Diabetes decreased from 15 to 10%, dyslipidaemia decreased from 20 to 18%, hypercholesterolaemia decreased from 32 to 21% and osteoarthropathy decreased from 25 to 13%., Conclusions: The intragastric balloon is safe and effective in overweight patients, helping to reduce progression to obesity and decreasing the prevalence of a number of important co-morbidities.

Monoclonal gammopathy of undetermined significance (MGUS) has been associated with an increased risk of thrombosis. We carried out a retrospective multicentre cohort study on 1491 patients with MGUS. In 49 patients (3.3%) MGUS was diagnosed after a thrombotic event. Follow-up details for a period of at least 12 months after diagnosis of MGUS were obtained in 1238 patients who had no recent history of thrombosis (<2 years) prior to diagnosis, for a total of 7334 years. During the follow-up, 33 of 1238 patients (2.7%) experienced thrombosis, with an incidence of 2.5 arterial events and 1.9 venous events per 1000 patient-years. Multivariate analysis showed increased risks of arterial thrombosis in patients with cardiovascular risk factors [hazard ratio (HR) 4.92, 95%confidence interval (CI) 1.42-17.04], and of venous thrombosis in patients with a serum monoclonal (M)-protein level >16 g/l at diagnosis (HR 3.08, 95%CI 1.01-9.36). No thrombosis was recorded in patients who developed multiple myeloma (n = 50) or other neoplastic diseases (n = 21). The incidence of arterial or venous thrombosis in patients with MGUS did not increase relative to that reported in the general population for similarly aged members. Finally, the risk of venous thrombosis did increase when the M-protein concentration exceeded >16 g/l., (© 2012 Blackwell Publishing Ltd.)

Objective: To assess the prevalence and geographic distribution of major cardiovascular risk factors in a large community-wide sample of the Italian population., Design: A cross-sectional survey. Standardized methods were used to collect and measure cardiovascular risk factors. Data were adjusted for survey weightings. Qualitative and quantitative variables were compared with parametric and non-parametric tests, as appropriate., Setting: Towns (n 193) across different Italian regions., Subjects: Unselected adults (n 24 213; 12 626 men; 11 587 women) aged 18-98 years (mean age 56·9 (sd 15·3) years), who volunteered to participate in a community-wide screening programme over a 2 d period in 2007., Results: Overall, the prevalence of major cardiovascular risk factors was: obesity, 22·7 % (women 18·9 %, men 26·1 %); overweight, 44·7 % (women 31·6 %, men 56·7 %); hypertension, 59·6 % (women 48·3 %, men 70·0 %); dyslipidaemia, 59·1 % (women 57·7 %, men 60·3 %); diabetes, 15·3 % (women 11·2 %, men 19·0 %) and smoking, 19·8 % (women 14·0 %, men 25·2 %). We found a high prevalence of unhealthy eating habits; fruit and vegetable consumption was below the recommended range in 60 % of the study population. Ninety per cent of the study population had more than one cardiovascular risk factor and 84 % had between two and five cardiovascular risk factors. There were differences among Italian macro-areas mainly for obesity, hypertension, dyslipidaemia and diabetes., Conclusions: The study provides alarming evidence on current prevalence data for major cardiovascular risk factors in a large sample of the Italian population. Particularly, obesity and hypertension represent a relevant public health problem. There is a pressing need for effective preventive health measures which must also take into account the differences among Italian macro-areas.

Background: The Multiple Intervention and Audit in Renal Diseases to Optimize Care (MAURO) study was a cluster randomized controlled trial in 22 renal clinics which aimed to assess the efficacy of a multimodal quality improvement intervention to increase compliance with guideline recommendations for prevention of chronic kidney disease (CKD) progression and cardiovascular (CV) complications. The trial aimed to test whether this multimodal intervention improved adherence to recommended targets for a series of surrogate indicators relevant to blood pressure (BP) control, sodium intake, proteinuria, dyslipidemia, anemia and calcium-phosphate alterations. The trial also tested whether the same intervention slowed CKD progression and prevented CV complications in CKD patients., Method: Twenty-two renal clinics were randomized to 2 arms: an intervention arm applying a multimethod quality improvement intervention and a control arm providing standard care. Surrogate indicators were measured to evaluate blood pressure (BP) control, sodium intake, proteinuria, dyslipidemia, anemia and calcium-phosphate alterations., Results: Notwithstanding the fact that the vast majority of patients enrolled in this study (95%) were being treated with antihypertensive drugs, BP goals at baseline (specific for proteinuria level and diabetes) were met only in 45% of nonproteinuric patients and in just 14% and 18% of proteinuric and diabetic patients, respectively. The use of diuretics in hypertensive patients was less than what was needed, and about 80% of patients showed a salt excretion >100 mmol/24 hours. Total and low-density lipoprotein cholesterol levels were out of target in over 40% of patients, but only about 60% of these were on statins. A large majority of CKD patients were obese or overweight. The proportion of smokers was relatively small (13%), and 37% of patients had quit smoking, indicating patients' awareness of the health risks of smoking., Conclusions: In our cohort, management of modifiable risk factors for CKD progression and CV disease could be substantially improved.

Background: We compared rates and case fatality from a population-based stroke register in Northern Italy between 1998 and 2004 to assess changes over time and to evaluate changes in case diagnosis and management., Methods: The WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease criteria were used to identify suspected fatal or nonfatal events occurring among residents 35-74 years of age. Data on in-hospital treatments, symptoms and diagnostic tools were extracted. Out-of-hospital deaths were also investigated. The annual average relative change (ARC) in death rate, attack rate and case fatality were derived from Poisson models., Results: Death rates due to ischemic stroke (IS) decreased [men: ARC -12.7, 95% confidence interval (CI) -21.3 to -3.2; women: ARC -14.0, 95% CI -23.3 to -3.5]. These reductions are attributable to decreases in case fatality; attack rates of nonfatal IS increased (men: ARC 3.6, 95% CI 0.5-6.7; women: ARC 4.1, 95% CI 0.0-8.2). IS patients showed a higher prevalence of dyslipidemia and hypertension and underwent MRI more frequently in 2004. Both findings may explain the increased proportions of less severe cases. Case fatality and attack rates for hemorrhagic strokes (HS) were stable, with an observed increased prevalence of patients under anticoagulant/antiplatelet treatments., Conclusions: In this low-IS-incidence population, death rates decreased substantially during the investigated period. More accurate diagnostic tools increase the probability of detecting less severe cases. HS remains a frequently fatal disease with a stable incidence., (Copyright © 2012 S. Karger AG, Basel.)

LDL apheresis (LDLa) is an invasive therapeutic tool to control qualitative and quantitative disorders of lipid metabolism. It is aimed at achieving a metabolic balance in association with lipid-lowering drugs in patients with severe, genetically determined or acquired dyslipidemia who do not reach clinically adequate LDL-cholesterol (LDL-C) levels (<70 mg/dL) despite appropriate lipid-lowering drug treatment. A poorly known dyslipidemia is constituted by elevation of lipoprotein (a) [Lp(a)], which appears to be genetically determined and not influenced by diet or lipid-lowering medication. An Lp(a) level exceeding 30 mg/dL is an independent risk factor for premature cardiovascular disease and cerebrovascular disease. Numerous data support the notion that cardiovascular risk reduction is related to the degree of reduction of LDL-C, and the progression of atherosclerosis can be delayed or reversed by intensive and continuous cholesterol-lowering treatment. After the introduction of HMG-CoA reductase inhibitors (statins), the clinical benefit of cholesterol-lowering treatment has received significant confirmation. However, this treatment has shown poor results in the most severe, genetically determined forms. LDLa is an intensive extracorporeal cholesterol-lowering treatment approach with well documented efficacy and safety. It has also shown effects not directly correlated with its lipid-lowering activity, such as antioxidant effects on oxidized LDL and antiinflammatory effects on the cytokine network, the endothelium and the coagulation system. Finally, data acquired by the Italian Multicenter Study on LDLa Working Group were highlighted and the new evidence in the literature discussed.

Purpose: The Italian national prevention plan 2005-2008 included 10-year cardiovascular risk (10-CR) assessment of the general population aged 35-69 years using the CUORE project risk score. General practitioners (GPs) were encouraged to collect data on risk factors and 10-CR and to contribute to the Cardiovascular Risk Observatory (CRO). The aim is to demonstrate feasibility and effectiveness of 10-CR assessment as a first step to implement primary preventive actions at the individual level., Methods: Data were collected using CUORE.EXE software, easily and freely downloadable by GPs from the CUORE project website (www.cuore.iss.it). CRO provides a web platform to analyse and compare data on 10-CR and risk factors at regional and national levels with the aim of supporting health policy decision processes., Results: From January 2007 to May 2010, 2,858 GPs downloaded cuore.exe; 139,269 CR assessments on 117,345 persons were sent to CRO. CR mean was 3.0% in women, 8.3% in men; 30% of men and 65% of women were at lower risk (CR < 3%), 9.2% of men and 0.4% of women were at high risk (CR ≥ 20%). Among those with at least two risk assessments (n = 5,948), 8% (95% CI 7-9%) shifted to a lower risk class after 1 year. Systolic blood pressure mean levels decreased by 1.6 mmHg (95% CI 1.2-2.1 mmHg), diastolic blood pressure by 0.9 mmHg (95% CI 0.5-1.3 mmHg), total cholesterol by 5.6 mg/dl (95% CI 4.3-6.8 mg/dl), and smokers prevalence by 3.5% (95% CI 2.5-4.6%); high-density lipoprotein cholesterol increased in women by 1 mg/dl (95% CI 0.5-1.4 mg/dl)., Conclusions: Data demonstrate that 10-CR assessment can be the first step to implement preventive actions in primary care.

Introduction: The prevalence of patients with 'borderline' levels of cardiovascular risk factors has been rarely investigated, being often reported in studies evaluating abnormal values of these parameters. The BORDERLINE study represents a pilot experience to primarily identify the prevalence of 'high-normal' conditions, such as pre-hypertension, lipid and glucose levels in the upper range of normality in the setting of general practice in Italy., Aim: The aim of this study was to evaluate the prevalence of patients with 'borderline' values of cardiovascular risk factors in Italy., Methods: Involved physicians were asked to evaluate the first 20 outpatients, consecutively seen in June 2009. Data were collected in a study-designed case-report form, in which physicians identified thresholds rather than reported absolute values of several clinical parameters. High-normal values were defined as follows: blood pressure (BP) 130-140/85-90 mmHg; total cholesterol 180-200 mg/dL; low-density lipoprotein cholesterol (LDL-C) 130-150 mg/dL; high-density lipoprotein cholesterol (HDL-C) 30-40 mg/dL in males and 40-50 mg/dL in females; triglycerides 130-150 mg/dL and fasting glucose 100-110 mg/dL., Results: Fifty-three Italian physicians provided valuable clinical data on 826 individual outpatients, among which 692 (83.7%, 377 women, mean age 60.9 ± 13.2 years, body mass index 26.6 ± 5.0 kg/m2) were included in the present analysis. Prevalence of borderline values of systolic BP and total cholesterol levels were at least comparable with those in the normal limits of the corresponding parameters, whereas prevalence of borderline diastolic BP, LDL-C, HDL-C, triglycerides and fasting glucose levels was significantly lower than that of normal values, but higher than that of abnormal values of the corresponding parameters., Conclusions: Using this sample of healthy subjects in the setting of general practice in Italy, our results demonstrated a relatively high prevalence of borderline values of cardiovascular risk factors, which was at least comparable with that of normal, but significantly higher than that of abnormal thresholds. These preliminary findings may prompt more extensive investigations in the area of 'borderline' cardiovascular risk. This information may, in fact, potentially enable the design of more effective prevention strategies in the future to limit the burden of cardiovascular disease in the general population in Italy. Received for publication 4 March 2011; accepted for publication 20 April 2011.

Background: Previous studies have reported that statin use was associated with reductions in cardiovascular morbidity and mortality among patients with dyslipidemia, even without established cardiovascular disease. However, inadequate adherence may reduce statins' protective effects., Objective: The aim of this work was to investigate whether an association exists between statin adherence when used as primary prevention and risk of subsequent ischemic heart disease (IHD)., Methods: People aged >or=18 years who were residents of Italy's Lombardy region and were newly treated with statins in 2002 to 2003 were assessed as part of a retrospective analysis of data from a health services database. Patients who were hospitalized for IHD during this period were identified with hospital discharge information from a health-services database; IHD-related hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes for acute myocardial infarction (410), acute and subacute forms of IHD (411), and/or codes concerning coronary revascularization (36.0-36.9). Four groups of patients were excluded: those with >or=1 lipid-lowering drug within 2 years before the index prescription (to limit the sample to treatment initiators); those who had been hospitalized for cardiovascular disease or had used medications for IHD or heart failure within 2 years before the index date (to limit the study to primary prevention); those who did not have >or=1 year of follow-up; and those who received only 1 dispensation of a statin during the first year after the index prescription. Follow-up continued until hospitalization for IHD or any other cardiovascular cause, death from any cause, emigration, or the end of the study period (June 30, 2007). The proportion of days covered (PDC) by therapy with statins was the exposure variable; it served as a proxy for adherence. PDC (and therefore adherence) was categorized as very low (or=75%) coverage. A proportional hazards model was fitted to estimate hazard ratio (HR) and 95% CIs for the association between time-dependent categories of PDC and time of IHD hospitalization, after correcting for covariates., Results: A group of 90,832 patients was included; during follow-up, 1480 patients experienced a hospitalization for IHD. After the Cox proportional hazards model was adjusted for age, sex, type of statin dispensed at index prescription, current use of other selected drugs (ie, antidiabetics, antihypertensives, digitalis or organic nitrates, or other cardiac medications), Charlson comorbidity index, and whether or not a given patient switched statins, those with low, intermediate, or high statin coverage had HR (95% CI) values of 0.85 (0.72-0.98), 0.82 (0.71-0.95), and 0.81 (0.71-0.94), respectively, compared with patients with very low coverage., Conclusions: In these Italian subjects without a history of cardiovascular disease, low, intermediate, and high levels of adherence to statin pharmaco-therapy were associated with lower risk of nonfatal IHD compared with those who had very low (

Background: The CardioRESET project was carried out in 2005 to evaluate the feasibility of a cardiovascular risk factor survey by general practitioners in Friuli Venezia Giulia, a north-eastern Italian region., Methods: We randomized 2701 subjects (1336 males and 1365 females), aged 35-74 years, from the general population. The family doctors surveyed the randomized population sample using the standardized methods of the Osservatorio Epidemiologico Cardiovascolare, a reference national survey., Results: The participation rate was 85.4% and all variables were recorded at least in 60% of subjects. Mean values of risk factors, prevalence of hypertension, dyslipidemia, diabetes and data on their control, smoking habits were comparable with data from the Osservatorio Epidemiologico Cardiovascolare; only the mean value of low-density lipoprotein cholesterolemia was higher in our region., Conclusions: This experience points out that in a small region it is possible to engage general practitioners to achieve a standardized surveillance of cardiovascular risk factors at a low cost.

Background: Dyslipidemia is a common metabolic complication in polycystic ovary syndrome (PCOS). The aim of this study was to determine if differences exist in dyslipidemia in women with PCOS from different ethnic and geographical backgrounds., Methods: This retrospective study evaluated the serum fasting lipid profiles of 106 women with PCOS from the United States and 108 women with PCOS from Italy evaluated at endocrinology clinics., Results: American women had higher mean body mass index than Italian women (36.1+/-8.6 vs 28.1+/-5.8 kg/m2, p<0.01). Low HDL-cholesterol was the most prevalent lipid abnormality in both populations. U.S. women had higher mean levels of serum total cholesterol, LDL-cholesterol, and triglycerides, and lower mean serum HDL-cholesterol. Most of these differences were due to differences in weight. After controlling for differences in weight and age, fasting serum triglycerides remained higher in U.S. women compared with Italian women [131.1 mg/dl, SE=7.8, 95% confidence interval =(115.7, 146.5) vs 99.3, SE=8.4, 95% confidence interval =(82.9, 115.8)]., Conclusions: Variations in body weight alone do not fully explain differences in dyslipidemia in women of diverse ethnic and geographical backgrounds. Genetic and environmental factors, such as diet and activity level, likely contribute to these differences.

Aim of This Study: To describe the extent to which hyperglycemia, hypertension, and dyslipidemia are currently detected, treated, and controlled in diabetic patients attending a network of urban community-based diabetic care clinics in Italy., Methods: The study population included 1078 consecutive patients with type 2 diabetes mellitus (47% women, mean age 67.6+/-9.8 years) visited at eight diabetic care clinics between 1 and 30 of November 2004. Values of glycosilated hemoglobin, blood pressure, and cholesterol subfractions, as well as clinical and medication data, were prospectively collected in all cases in a computerized database., Results: Despite a high prevalence of hypertension (66.6%), only 29.6% of patients met the treatment goal of a systolic blood pressure <130 mmHg, while a diastolic blood pressure <80 mmHg was reached by 38.6% of the study cohort. Optimal LDL cholesterol values (<100mg/dl) were present in just 25.5% of cases. Values of glycosilated hemoglobin <7% were present in 57.8% of patients., Conclusions: We conclude that adherence to current guidelines for cardiovascular prevention and cardiovascular risk factor control represent an exception in diabetic patients attending community-based diabetic care clinics. Major efforts are required to improve the quality of health care currently delivered to diabetic patients.

Objectives: Advanced diabetic nephropathy (DN) is characterized by a marked development of cardiovascular and renal disease. These patients are frequently managed by different health professionals with the consequence that the quality of care may differ substantially. To compare the management of cardiovascular risk factors in patients with type 2 DN and an estimated glomerular filtration rate (GFR) of 15-60 ml/min per 1.73 m2 followed in nephrology, diabetology and primary care., Methods: This multicentre cross-sectional study verified the control of blood pressure (BP), total cholesterol, triglycerides, glycosylated haemoglobin A1c (HbA1c) and haemoglobin in patients exclusively followed in either nephrology (n = 266), diabetology (n = 246) or primary care (n = 195) of the same metropolitan area for at least 1 year., Results: Primary care patients were older and had a greater prevalence of previous cardiovascular events. The GFR was lower in nephrology than in diabetology and primary care (33 +/- 13 versus 47 +/- 9 and 40 +/- 12 ml/min per 1.73 m2, P < 0.0001). The prevalence of BP target (< 130/80 mmHg) was similarly low in nephrology, diabetology and primary care (14, 13 and 10%, P = 0.421) probably because of insufficient prescription of diuretics and low-salt diet. Whereas the prevalence of the triglycerides target was similar, that of total cholesterol (< 200 mg/dl) was larger in diabetology (63%) than in nephrology and primary care (59 and 46%, P = 0.003) because of greater statin prescription in hypercholesterolemic individuals (70, 50 and 41%, respectively, P = 0.002). The attainment of HbA1c less than 7% was less frequent in diabetology (32%) than in nephrology and primary care (61 and 46%, P = 0.0003) despite a more frequent prescription of insulin/oral agents in diabetology. The control of anaemia was better in diabetology. Multivariate analysis adjusted for the patient case-mix and physician-level clustering confirmed these differences except for anaemia., Conclusion: Patients with advanced DN, despite the worst renal and cardiovascular prognosis, are at high risk of being under-treated independently of the type of clinical setting.

To identify HIV-associated episodes of gynecomastia occurred during antiretroviral therapy in a cohort of around 1,000 patients, and to investigate potential correlations with demographic and epidemiological variables, clinical-laboratory markers of HIV disease, metabolic disturbances, and antiretroviral treatment, a cross-sectional survey of 1.007 patients treated for at least 12 months (669 males: 66.4%), identified all subjects with true (ultrasonography-confirmed) gynecomastia, after exclusion of all other predisposing conditions. Special attention was paid to eventual metabolic alterations, including lipodystrophy syndrome, dyslipidemia, and hyperglycemia, and administered antiretrovirals. Fifteen of the 516 evaluable male subjects (2.9%), developed gynecomastia when aged 12-58 years. A concurrent lipodystrophy was present in all cases, while hypertriglyceridemia, hypercholesterolemia, and hyperglycemia were found in 11, 6, and 3 patients, respectively. Duration of seropositivity and time from start of antiretroviral therapy varied significantly, and no correlation was found with HIV disease progression, but 5 patients never received protease inhibitors, while an efavirenz-based treatment apparently prompted gynecomastia in 4 protease inhibitor-naive patients, and worsened this sign in other 4 patients switching from a protease inhibitor-based HAART. One patient developed gynecomastia while on isolated nucleoside analogue therapy. In the whole patient group, stavudine proved the nucleoside analogue administered more frequently and for a more prolonged time. During the follow-up, no significant ameliorament of gynecomastia was observed despite eventual therapeutic changes. Gynecomastia, as an emerging untoward event of treated HIV infection, deserves further investigation, from an epidemiological, clinical, and especially pathogenetic point of view. The frequent association with metabolic abnormalities suggests some common ethiologic pathway with other HAART-related disturbances.